Squamous cell carcinoma of the head and neck (HNSCC) remains a cancer with a very poor prognosis. Current standard treatment protocols have significant morbidity, and this has led to continuing investigation of potential alternative and less toxic therapies. Curcumin, commonly known as the spice turmeric, is derived from the East Indian plant Curcuma longa. It is used as a flavoring agent and also has been used in Ayurvedic medicine for over 6,000 years. Curcumin is an FDA approved substance with chemopreventive and anticancer properties. We have studied the effect of curcumin on HNSCC in vitro and in vivo and have found suppression of cell growth. The objective of this project is to suppress the growth of HNSCC using curcumin. We will study a liposomal delivery method for curcumin treatment and also determine the effect of curcumin treatment on IL-6 and IL-8 levels both in vitro and in vivo. Finally, we plan to determine whether a there is a synergistic antitumor effect using curcumin in combination with cisplatin in HNSCC. The specific aims of this project are: 1) To treat HNSCC cells with increasing doses of liposomal curcumin, assess cell viability, and determine the effect on IL-6 and IL-8 levels; 2) To grow HNSCC xenograft tumors in nude mice and treat mice with intravenous liposomal curucmin, injected via the tail vein. We will compare the suppressive effect of intravenous liposomal curcumin with topical curcumin paste on the HNSCC xenografts; 3) To grow HNSCC xenograft tumors in nude mice, treat them with curcumin in combination with cisplatin, and determine the effect on tumor growth. The ultimate goal of this research is to develop adjuvant treatments for patients with head and neck cancer, particularly those who have failed conventional treatment modalities. Currently, such patients often require debilitating surgery and/or radiation and chemotherapy. In order to accomplish this goal, we are attempting to identify an adjuvant treatment using a dietary supplement with potential anticancer properties. Development of curcumin as an alternative therapy for head and neck squamous cell carcinoma would greatly benefit the public's health, as current treatment modalities for this devastating disease, including major surgical resection, radiation, and chemotherapy have significant morbidity. In addition, there is benefit in the potential use of curcumin as a chemopreventive agent in high-risk patients, such as heavy smokers or those with a history of previous head and neck cancer. Principal Investigator/Program Director (Last, First, Middle): Wang, Marilene Beth Current treatment protocols for advanced head and neck cancer often entail a disfiguring and risky surgical operation. In addition, radiation therapy and chemotherapy used in conjunction with the surgery result in tremendous morbidity for patients with HNSCC. Despite our best efforts, survival rates for late stage HNSCC remain dismal. It is apparent that a different approach to treatment is needed. Curcumin as an alternative/complementary therapy offers obvious advantages over the current standard treatment protocols, which involve the morbidities of surgery and radiation. The ultimate goal of this research is to develop adjuvant treatments for patients with head and neck cancer, particularly patients with advanced cancers or cancers which have failed conventional treatment modalities. Currently, such patients often require debilitating surgery and/or radiation and chemotherapy. Others are left with few options other than palliative and/or hospice care. In order to accomplish this goal, we are attempting to identify an innovative alternative treatment using a dietary supplement with potential anticancer properties. Curcumin, possibly in combination with the standard chemotherapeutic agent cisplatin, holds promise as a valuable treatment option for patients with HNSCC PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page 1 Continuation Format Page [unreadable] [unreadable] [unreadable]